고령의 대장암 환자의 회복과정에서 면역학적 변화와 근감소증의 관계 및 근감소증이 회복에 미치는 영향

Abstract

Background Colorectal cancer is one of the most frequent malignancies, with a rising proportion of elderly patients in an aging society. Therefore, efforts to provide individualized and appropriate treatment for elderly patients are also increasing. Cancer-related inflammation affects cancer progression and prognosis, and immunological variables that influence this process, as well as ones that influence recovery following surgery, are critical. In this study, we attempted to support the establishment of an individualized treatment plan for elderly patients by analyzing modifiable elements among various parameters impacting the treatment. Methods In retrospective study, we reviewed the records of colorectal cancer patients (10,271 patients) who received surgical treatment in multi-centers including 8 tertiary centers between March 2018 and September 2020 and also reviewed record of patients who received curative resection for colorectal cancer between January 20005 and November 2011 at Asan Medical Center. In prospective study, total 40 patients who received radical resection for colon cancer between September and November 2023 at Asan Medical Center was involved. We included colon cancer patients treated with surgery, diagnosed with adenocarcinoma histologically and having information regarding preoperative status with abdominopelvic CT. Routine blood sampling and Immunologic tests including interleukin-6 (IL-6), natural killer cell (NK cell), and tumor necrosis factor-alpha (TNF-alpha) were performed at preoperative day, post operative 3rd day (POD#3), and outpatient clinic day (about postoperative 21th day (POD#21)). We attempted to assess the patients’ subjective health level using a simple questionnaire, EuroQol group- 5 dimension- 3 level (EQ-5D-3L). The sarcopenia was evaluated by the artificial intelligence software system and defined as an SMI < 41cm2/m2 in women and SMI < 43 cm2/m2 in men with a body mass index (BMI) < 25kg/m2, and < 53 cm2/m2 in men with a BMI ≥ 25 kg/m2. The primary end point was’ recovery’ represented by hospital stay and secondary end point was ‘EQ-5D-3L index value’. ‘Recovery’ was evaluated by hospital stay and readmission within 30 days after discharge. Patients who had a shorter-than-average hospital stay rated their recovery as fast, whereas those who had a longer-than-average hospital stay or readmitted within 30 days after discharge rated their recovery as slow. Results In retrospective cohort study of multicenter data, American society of anesthesiologists physical status classification (ASA classification), clinical T (cT) stage, clinical N (cN) stage was associated with postoperative recovery in elderly patients (ASA classification; OR 0.92; 95%CI, 0.89-0.96, P <0.001; cT; OR 0.91; 95%CI, 0.87-0.96, P <0.001; cN; OR 0.92; 95%CI, 0.88-0.96, P <0.001). Furthermore, patient who were discharged within 7 days and were not readmitted within 30days were at lower risk of recurrence (HR 0.61; 95%CI, 0.48-0.77, P <0.001). In retrospective cohort study, neutrophil-lymphocyte ratio (NLR), albumin and sarcopenia were related with recovery after operation in elderly patients. (NLR; OR 0.52; 95%CI, 0.28-0.97, P=0.041; albumin; OR 2.01; 95%CI, 1.06-3.79, P=0.032; sarcopenia; OR 0.44; 95%CI, 0.21-0.94, P=0.034). Fast recovery represented by shorter hospital stay without readmission within 30 days after discharge, pathologic N (pN) stage, and lymphovascular invasion (Lvi) was associated OS (HR 0.64; 95%CI, 0.42- 0.97; P=0.036, HR 1.61; 95%CI, 1.04-2.47; P=0.032, HR 1.63; 95%CI, 1.06-2.50; P=0.025, respectively). In prospective cohort study, of 40 patients, 24 (60.0%) were male and the mean age was 66.3 (±13.0) years old. About 60% of all patients had more than one comorbidity. (62.5%, 25 patients). The mean hospital day was 5 days most of all discharged within 5 days (85%, 34 patients). There was no significant difference in clinicopathologic characteristics associated with recovery between non-elderly and elderly-groups. Only ASA classification was associated with recovery (OR: 0.13; 95% CI, 0.01- 1.15, P=0.066) in the entire group. Likewise, in elderly group, the only risk factor for recovery was the ASA classification; all other factors including NLR, albumin, and sarcopenia had no significant impact on recovery (P=0.358, P=0.539, and P=0.662, respectively). There were no significant variables associated with recovery and sarcopenia in the distribution of immunologic factors including IL-6, NK cell, and TNF-alpha regardless of the timing, preoperative, POD#3 and POD#21. However, levels of preoperative IL-6 and NK cell at preoperative, POD#3, and POD#21 were significantly higher in elderly group than non-elderly group. In addition, patients with higher pre-operative EQ-5D-3L index values were more prevalent in the fast recovery group (64.7% vs. 33.3% in the elderly patient group), though it was not significant statistically (P=0.701) Conclusion According to the results of this study, NLR, albumin and sarcopenia were associated with postoperative recovery in elderly patients and correlation between recovery and oncologic outcomes was also identified. In addition, no significant immunologic variables were identified to be associated with recovery or sarcopenia, however, elderly patients tended to have higher NK cell and IL-6 levels. The NK cell, which were not lower in the elderly group, demonstrated that, in contrast to the non-elderly group, elderly patients do not always have poor outcome prior and after surgery. As a result, we have to focus on improving the recovery-related factors discussed in this study before surgery, and further research is needed to ascertain whether variables evaluated in this study or other than the cytokines used in this study was also affect recovery. Keywords: colon cancer, immune, sarcopenia, aged